Ibrutinib + Stem Cell Transplant for Lymphoma

Not currently recruiting at 320 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: National Cancer Institute (NCI)

Must not be taking: Strong CYP3A inhibitors, Strong CYP3A inducers, HIV protease inhibitors, Zidovudine

Disqualifiers: Active CNS involvement, Hepatic impairment, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 6

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines whether adding ibrutinib to high-dose chemotherapy and stem cell transplant can enhance treatment for individuals with diffuse large B-cell lymphoma that has recurred or is unresponsive to treatment. Ibrutinib may inhibit cancer cell growth by blocking a necessary protein. The trial compares outcomes between participants receiving ibrutinib and those receiving a placebo, alongside their standard treatment. Individuals who have experienced at least partial success with previous treatments for this type of lymphoma might be suitable candidates for this trial. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants an opportunity to contribute to potential new treatment options.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, you should not require chronic use of strong CYP3A inhibitors or inducers, and you should not need therapeutic doses of steroids unless necessary. It's best to discuss your current medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Previous studies have generally shown that patients tolerate ibrutinib well. Some side effects, such as tiredness, diarrhea, and nausea, have been reported, but these are often mild. Serious side effects, though less common, can include infections and bleeding.

The FDA has already approved ibrutinib for other conditions, indicating that its safety has been thoroughly studied. However, individual experiences may vary, so discussing any concerns with a doctor is important. This treatment aims to help patients with lymphoma by blocking a protein that cancer cells need to grow. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for lymphoma?

Researchers are excited about ibrutinib for lymphoma because, unlike traditional treatments that rely heavily on chemotherapy alone, ibrutinib targets specific proteins involved in the growth of cancer cells. This unique mechanism of action can provide a more focused approach, potentially leading to better outcomes with fewer side effects. Moreover, ibrutinib is taken orally, which can be more convenient compared to intravenous chemotherapy. This combination of targeted action and ease of use makes ibrutinib a promising option for improving lymphoma treatment.

What evidence suggests that this trial's treatments could be effective for diffuse large B-cell lymphoma?

This trial will compare the effectiveness of adding ibrutinib to a stem cell transplant regimen versus a placebo in patients with diffuse large B-cell lymphoma. Research has shown that adding ibrutinib to treatment can help patients with certain types of lymphoma by blocking a protein that cancer cells need to grow. Studies have found that using ibrutinib along with stem cell transplants can be more effective than using standard chemotherapy alone. In younger patients with mantle cell lymphoma, ibrutinib has led to better outcomes, although it may cause more side effects. While this trial focuses on diffuse large B-cell lymphoma, the positive results from similar conditions suggest potential benefits. ^{1 3 4 6 7}

Who Is on the Research Team?

Charalambos B Andreadis

Principal Investigator

Alliance for Clinical Trials in Oncology

Are You a Good Fit for This Trial?

Adults with relapsed or refractory diffuse large B-cell lymphoma eligible for stem cell transplant can join. They must have responded at least partially to prior chemotherapy, be in good physical condition, and not have severe heart, lung, liver issues or active infections like hepatitis B/C or HIV with complications. Pregnant/nursing individuals and those on certain drugs are excluded.

Inclusion Criteria

I am not on high doses of steroids, or can stop them 14 days before treatment.

I am not using HIV protease inhibitors for my HIV treatment.

Patients cannot have:

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Conditioning Regimen

Patients receive either the BEAMi or CBVi regimen, including ibrutinib or placebo, followed by high-dose chemotherapy to prepare for stem cell transplant

1 week

Daily visits for chemotherapy administration

Transplant

Patients undergo autologous hematopoietic progenitor cell or bone marrow transplant

1 day

Inpatient procedure

Continuation Regimen

Patients receive ibrutinib or placebo for 12 cycles, starting 30-60 days post-transplant, in the absence of disease progression or unacceptable toxicity

12 months

Monthly visits for treatment cycles

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 60 months

Every 6 months

What Are the Treatments Tested in This Trial?

Interventions

• Autologous Bone Marrow Transplantation
• Autologous Hematopoietic Stem Cell Transplantation
• Ibrutinib

Trial Overview The trial is testing if adding the drug Ibrutinib to standard high-dose chemotherapy before and after a stem cell transplant can improve outcomes in patients with difficult-to-treat lymphoma compared to a placebo.

How Is the Trial Designed?

Group I: Arm I (ibrutinib, chemotherapy, autoHCT) Experimental Treatment 10 Interventions

CONDITIONING REGIMEN: Investigators may choose to use either the BEAMi or CBVi regimen. BEAMi: Patients receive ibrutinib PO on days -6 to -1 or days -7 to -2 if a day of rest is planned, carmustine IV over 2 hours on day -6, etoposide IV BID over 1-2 hours and cytarabine IV BID over 1-2 hours on days -5 to -2, and melphalan IV over 20-30 minutes on day -1. CBVi: Patients receive ibrutinib PO on days -6 to -1 or days -7 to -2 if a day of rest is planned, carmustine IV over 2 hours on day -6, etoposide IV over 4 hours on day -4, and cyclophosphamide IV on day -2. TRANSPLANT: In both arms, patients undergo autologous hematopoietic progenitor cell or bone marrow transplant on day 0. CONTINUATION REGIMEN: Beginning 30-60 days after transplant, patients receive ibrutinib PO on days 1-28. Treatment repeats every 28 days for 12 cycles in the absence of disease progression or unacceptable toxicity.

Group II: Arm II (placebo, chemotherapy, autoHCT) Placebo Group 10 Interventions

CONDITIONING REGIMEN: Patients receive placebo PO on days -6 to -1 and receive 1 of the 2 conditioning regimens as in Arm I. TRANSPLANT: Patients undergo autologous hematopoietic progenitor cell or bone marrow transplant on day 0. CONTINUATION REGIMEN: Beginning 30-60 days after transplant, patients receive placebo PO on days 1-28. Treatment repeats every 28 days for 12 cycles in the absence of disease progression or unacceptable toxicity. Patients experiencing disease progression may crossover Arm I.

Ibrutinib is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Imbruvica for:

• Chronic lymphocytic leukemia
• Mantle cell lymphoma
• Waldenström's macroglobulinemia
• Marginal zone lymphoma
• Graft-versus-host disease

Approved in United States as Imbruvica for:

• Chronic lymphocytic leukemia/small lymphocytic lymphoma
• Mantle cell lymphoma
• Waldenström's macroglobulinemia
• Marginal zone lymphoma
• Graft-versus-host disease

Approved in Canada as Imbruvica for:

• Chronic lymphocytic leukemia
• Mantle cell lymphoma
• Waldenström's macroglobulinemia
• Marginal zone lymphoma

Approved in Japan as Imbruvica for:

• Chronic lymphocytic leukemia
• Mantle cell lymphoma
• Waldenström's macroglobulinemia

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Ibrutinib is a targeted therapy specifically designed for treating chronic lymphocytic leukemia (CLL), which is a type of cancer that affects the blood and bone marrow.

This novel treatment works by inhibiting Bruton's tyrosine kinase (BTK), a key enzyme that helps cancer cells survive and proliferate, leading to improved patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ibrutinib (imbruvica): a novel targeted therapy for chronic lymphocytic leukemia. Parmar, S., Patel, K., Pinilla-Ibarz, J.[2021]

Ibrutinib is a powerful oral medication that effectively treats relapsed/refractory mantle cell lymphoma (MCL) and chronic lymphocytic leukaemia (CLL), showing high response rates and significantly improving survival outcomes, especially in patients with poor prognostic factors like chromosome 17 deletion (del 17p).

The drug has a good safety profile, with less than 10% of patients discontinuing treatment due to side effects, making it a promising option for patients with these types of blood cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ibrutinib: a review of its use in patients with mantle cell lymphoma or chronic lymphocytic leukaemia. Kim, ES., Dhillon, S.[2022]

Ibrutinib is an effective oral treatment for patients with relapsed/refractory mantle cell lymphoma (MCL) and chronic lymphocytic leukaemia (CLL), showing a 68% overall response rate in MCL and significant improvements in progression-free survival and overall survival in CLL patients, including those with specific genetic mutations.

The drug has a good safety profile, with less than 10% of patients discontinuing treatment due to adverse effects, making it a promising option for patients with various B-cell malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Ibrutinib: A new drug of B-cell malignancies]. Thieblemont, C.[2021]

Ibrutinib is an effective treatment for chronic lymphocytic leukaemia (CLL) and small lymphocytic lymphoma (SLL), showing better outcomes than traditional therapies like chlorambucil and ofatumumab in phase III trials involving elderly and previously-treated patients.

The drug has a good safety profile, although it can cause some adverse effects like bleeding and atrial fibrillation; it is recommended in treatment guidelines for patients with high-risk disease, including those with specific genetic mutations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ibrutinib: A Review in Chronic Lymphocytic Leukaemia. Deeks, ED.[2021]

Ibrutinib is a first-in-class oral Bruton's tyrosine kinase inhibitor that effectively blocks B-cell signaling, leading to reduced proliferation and increased cell death in B cell malignancies, including chronic lymphocytic leukaemia (CLL) and mantle cell lymphoma (MCL).

It has received FDA approval for treating MCL in previously treated patients based on phase Ib/II study results and is currently undergoing further phase III trials for CLL, diffuse large B cell lymphoma (DLBCL), and other B cell cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ibrutinib: first global approval. Cameron, F., Sanford, M.[2022]

Ibrutinib (Imbruvica) is now approved for treating graft-versus-host disease in pediatric patients aged one year and older who have not responded to other systemic therapies, highlighting its efficacy in a challenging patient population.

The treatment carries significant risks, including severe side effects like hemorrhage, infections, and cardiac issues, necessitating careful monitoring and education for patients and caregivers about these potential adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drug Receives New Indication for Pediatric Graft-Versus-Host Disease. Aschenbrenner, DS.[2023]

Citations

1. thelancet.com thelancet.com/journals/lancet/article/PIIS0140-6736(24)00184-3/fulltext

Ibrutinib combined with immunochemotherapy with or ... The results of the TRIANGLE trial confirm superior efficacy by the addition of ibrutinib to pre-trial standard treatment of younger, transplant- ...

2. jnj.com jnj.com/innovativemedicine/us/news-center/oncology/european-commission-approves-imbruvica-ibrutinib-as-the-first-targeted-therapy-for-patients-with-previously-untreated-mantle-cell-lymphoma-who-would-be-eligible-for-autologous-stem-cell-transplant

European Commission approves IMBRUVICA® (ibrutinib) ... Ibrutinib is the first approved Bruton's tyrosine kinase (BTK) inhibitor to demonstrate statistically meaningful outcomes versus autologous ...

3. ashpublications.org ashpublications.org/bloodneoplasia/article/2/3/100128/537696/Real-world-outcomes-with-ibrutinib-in-relapsed-or

Real-world outcomes with ibrutinib in relapsed or refractory ... In conclusion, real-world outcomes after initiation of ibrutinib for R/R MCL were poorer than observed in clinical trials, and dose-limiting ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38705160/

a three-arm, randomised, open-label, phase 3 superiority ... Adding ibrutinib to first-line treatment resulted in superior efficacy in younger mantle cell lymphoma patients with increased toxicity when given after ASCT.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT02443077

NCT02443077 | Ibrutinib Before and After Stem Cell ... This randomized phase III trial studies ibrutinib to see how well it works compared to placebo when given before and after stem cell transplant in treating ...

6. ema.europa.eu ema.europa.eu/en/documents/variation-report/imbruvica-h-c-003791-ii-0092-epar-assessment-report-variation_en.pdf

Imbruvica; INN-Ibrutinib - EMA Median OS for patients with MCL was recently presented to be about 5 years, in a non-selected nationwide cohort (n=1367, diagnosed 2006-2018 in ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7968880/

Real‐world outcomes of ibrutinib therapy in Korean ... Real‐world outcomes of ibrutinib therapy in Korean patients with relapsed or refractory mantle cell lymphoma: a multicenter, retrospective analysis